Sućur Alan, Katavić Vedran, Kelava Tomislav, Jajić Zrinka, Kovačić Natasa, Grčević Danka
Department of Physiology and Immunology, University of Zagreb School of Medicine, Šalata 3b, Zagreb, 10000, Croatia.
Int Orthop. 2014 Sep;38(9):1893-903. doi: 10.1007/s00264-014-2386-y. Epub 2014 Jun 10.
The inflammatory milieu favors recruitment and activation of osteoclasts, and leads to bone destruction as a serious complication associated with arthritis and with other inflammatory processes. The frequency and activity of osteoclast progenitors (OCPs) correspond to arthritis severity, and may be used to monitor disease progression and bone resorption, indicating the need for detailed characterization of the discrete OCP subpopulations. Collectively, current studies suggest that the most potent murine bone marrow OCP population can be identified among lymphoid negative population within the immature myeloid lineage cells, as B220(-)CD3(-)CD11b(-/lo)CD115(+)CD117(+)CX3CR1(+) and possibly also Ter119(-)CD11c(-)CD135(lo)Ly6C(+)RANK(-). In peripheral blood the OCP population bears the monocytoid phenotype B220(-)CD3(-)NK1.1(-)CD11b(+)Ly6C(hi)CD115(+)CX3CR1(+), presumably expressing RANK in committed OCPs. Much less is known about human OCPs and their regulation in arthritis, but the circulating OCP subset is, most probably, comprised among the lymphoid negative population (CD3(-)CD19(-)CD56(-)), within immature monocyte subset (CD11b(+)CD14(+)CD16(-)), expressing receptors for M-CSF and RANKL (CD115(+)RANK(+)). Our preliminary data confirmed positive association between the proportion of peripheral blood OCPs, defined as CD3(-)CD19(-)CD56(-)CD11b(+)CD14(+), and the disease activity score (DAS28) in the follow-up samples from patients with psoriatic arthritis receiving anti-TNF therapy. In addition, we reviewed cytokines and chemokines which, directly or indirectly, activate OCPs and enhance their differentiation potential, thus mediating osteoresorption. Control of the activity and migratory behaviour of OCPs as well as the identification of crucial bone/joint chemotactic mediators represent promising therapeutic targets in arthritis.
炎症环境有利于破骨细胞的募集和激活，并导致骨破坏，这是与关节炎及其他炎症过程相关的严重并发症。破骨细胞祖细胞（OCPs）的频率和活性与关节炎严重程度相关，可用于监测疾病进展和骨吸收情况，这表明需要对离散的OCP亚群进行详细表征。总体而言，目前的研究表明，在未成熟髓系谱系细胞中的淋巴细胞阴性群体中，可以鉴定出最有效的小鼠骨髓OCP群体，即B220(-)CD3(-)CD11b(-/lo)CD115(+)CD117(+)CX3CR1(+)，也可能是Ter119(-)CD11c(-)CD135(lo)Ly6C(+)RANK(-)。在外周血中，OCP群体具有单核细胞样表型B220(-)CD3(-)NK1.1(-)CD11b(+)Ly6C(hi)CD115(+)CX3CR1(+)，推测在成熟的OCP中表达RANK。关于人类OCP及其在关节炎中的调节知之甚少，但循环中的OCP亚群很可能包含在未成熟单核细胞亚群（CD11b(+)CD14(+)CD16(-)）中的淋巴细胞阴性群体（CD3(-)CD19(-)CD56(-)）中，表达M-CSF和RANKL的受体（CD115(+)RANK(+)）。我们的初步数据证实，在接受抗TNF治疗的银屑病关节炎患者的随访样本中，外周血OCPs（定义为CD3(-)CD19(-)CD56(-)CD11b(+)CD14(+)）的比例与疾病活动评分（DAS28）之间存在正相关。此外，我们综述了直接或间接激活OCPs并增强其分化潜能从而介导骨吸收的细胞因子和趋化因子。控制OCPs的活性和迁移行为以及鉴定关键的骨/关节趋化介质是关节炎中有前景的治疗靶点。
